PIBRENTASVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C57H65F5N10O8
Molecular Weight	1113.1802
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@H](C)[C@H](NC(=O)OC)C(=O)N1CCC[C@H]1C2=NC3=CC([C@H]4CC[C@@H](N4C5=CC(F)=C(N6CCC(CC6)C7=CC=C(F)C=C7)C(F)=C5)C8=C(F)C=C9NC(=NC9=C8)[C@@H]%10CCCN%10C(=O)[C@@H](NC(=O)OC)[C@@H](C)OC)=C(F)C=C3N2

InChI

InChIKey=VJYSBPDEJWLKKJ-NLIMODCCSA-N

InChI=1S/C57H65F5N10O8/c1-29(77-3)49(67-56(75)79-5)54(73)70-19-7-9-47(70)52-63-41-25-35(37(59)27-43(41)65-52)45-15-16-46(72(45)34-23-39(61)51(40(62)24-34)69-21-17-32(18-22-69)31-11-13-33(58)14-12-31)36-26-42-44(28-38(36)60)66-53(64-42)48-10-8-20-71(48)55(74)50(30(2)78-4)68-57(76)80-6/h11-14,23-30,32,45-50H,7-10,15-22H2,1-6H3,(H,63,65)(H,64,66)(H,67,75)(H,68,76)/t29-,30-,45-,46-,47+,48+,49+,50+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C57H65F5N10O8
Molecular Weight	1113.1802
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf | https://www.mavyret.com/ | https://www.ncbi.nlm.nih.gov/pubmed/28929412

Pibrentasvir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS5A inhibitor that targets the the viral RNA replication and viron assembly. NS5A is a phosphoprotein that plays an essential role in replication, assembly and maturation of infectious viral proteins. The basal phosphorylated form of NS5A, which is maintained by C-terminal serine cluster, is key in ensuring its interaction with the viral capsid protein, or the core protein. By blocking this interaction, pibrentasvir inhibits the assembly of proteins and production of mature HCV particles. In the United States and Europe, Pibrentasvir is approved for use with glecaprevir as the combination drug glecaprevir/pibrentasvir (trade name Mavyret in the US and Maviret in the EU) for the treatment of hepatitis C. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Nonstructural protein 5A 11 Target ID: CHEMBL3307224 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/28193664	Inhibitor 8297		0.0014 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: https://www.mavyret.com/ https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100217/mavyret-glecaprevir-and-pibrentasvir-	Primary		Approved 8429	MAVYRET Approved Use MAVYRET is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both. Launch Date 2017

C_max

Value	Dose	Analyte	Population
31 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
324 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.68 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
123 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
167 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
223 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	405 mg single, oral dose: 405 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
343 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
71.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
64.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
87.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
180 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2170 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
54.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
881 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.56 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1040 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
118 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1630 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	405 mg single, oral dose: 405 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2560 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
408 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
474 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
594 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
20.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	180 mg 1 times / day multiple, oral dose: 180 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	1.5 mg single, oral dose: 1.5 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	405 mg single, oral dose: 405 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
17.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28464496	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	PIBRENTASVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209394s010lbl.pdf	unknown, oral		PIBRENTASVIR plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 1 times / day multiple, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28464496	healthy, 18-55 years n = 8 Health Status: healthy Age Group: 18-55 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/28464496	Sources: https://pubmed.ncbi.nlm.nih.gov/28464496
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28464496	healthy, 18-55 years n = 6 Health Status: healthy Age Group: 18-55 years Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28464496	Sources: https://pubmed.ncbi.nlm.nih.gov/28464496

Sourcing

Vendor/Aggregator	ID	URL
Aaron Chemicals	AR01E7AY	http://www.aaronchem.com/1353900-92-1
Ambeed	A275632	https://www.ambeed.com/products/1353900-92-1.html
BioSynth	J-690144	https://www.biosynth.com/en/products/all-products/products/J-690163.html
CSNpharm	CSN19731	https://www.csnpharm.com/products/pibrentasvir.html
Chem Scene	CS-8135	http://www.chemscene.com/1353900-92-1.html
Chemspace	CSSB02125554574	https://chem-space.com/CSSB02125554574
DC Chemicals	DC10728	http://www.dcchemicals.com/product_show-Pibrentasvir.html
Excenen	EX-A865	http://www.excenen.com/searchresultlist.php?id=1353900-92-1
Lan Pharmatech	LAN-B70427	http://www.lanpharmatech.com/product-9?_keywords=LAN-B70427
MolPort	MolPort-046-701-598	https://www.molport.com/shop/molecule-link/MolPort-046-701-598
MuseChem	I008412	https://www.musechem.com/product/I008412.html
Selleck Chemicals	S9641	http://www.selleckchem.com/products/pibrentasvir-abt-530-.html
Smolecule	S539626	http://www.smolecule.com/products/s539626
THE BioTek	bt-280290	https://www.thebiotek.com/product/inhibitors/bt-280290
eNovation Chemicals	D663137	https://www.enovationchem.com/ProductDetails.asp?ProductID=D663137

PubMed

Title	Date	PubMed
In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir.	2017 May	28193664
Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1-7 and Escape Variants.	2018 Apr	29274866
Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan.	2018 Feb	29180522
Glecaprevir + pibrentasvir (ABT493 + ABT-530) for the treatment of Hepatitis C.	2018 Jan	29187007

Patents

Sample Use Guides

In Vivo Use Guide

MAVYRET is a fixed-dose combination product containing glecaprevir 100 mg and pibrentasvir 40 mg in each tablet. The recommended oral dosage of MAVYRET is three tablets (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) taken once daily with food.

Route of Administration: Oral

In Vitro Use Guide

According to HCV replicon assays, pibrentasvir has EC50 values ranging from 0.08-4.6 nM agaisnt laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a, or EC50 values of 0.5-4.3 pM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4b, 4d, 5a, 6a, 6e and 6p.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:27:43 GMT 2023` Edited by `admin` on `Sat Dec 16 09:27:43 GMT 2023`
Record UNII	2WU922TK3L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIBRENTASVIR

Official Name

English

Pibrentasvir [WHO-DD]

Common Name

English

ABT-530

Code

English

MAVYRET COMPONENT PIBRENTASVIR

Common Name

English

PIBRENTASVIR [ORANGE BOOK]

Common Name

English

PIBRENTASVIR [USAN]

Common Name

English

PIBRENTASVIR [JAN]

Common Name

English

PIBRENTASVIR [MI]

Common Name

English

DIMETHYL N,N'-(((2R,5R)-1-(3,5-DIFLUORO-4-(4-(4-FLUOROPHENYL)PIPERIDIN-1-YL)PHENYL)PYRROLIDINE-2,5-DIYL)BIS((6-FLUORO-1H-BENZIMIDAZOLE-5,2-DIYL)((2S)-PYRROLIDINE-2,1-DIYL)((2S,3R)-3-METHOXY-1-OXOBUTANE-1,2-DIYL)))BISCARBAMATE

Systematic Name

English

A-1325912.0

Code

English

pibrentasvir [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

550516